Gene transcription alterations associated with decrease of ethanol intake induced by naltrexone in the brain of...

Area of Science:

• Neuroscience
• Pharmacology
• Genetics

Background:

• Naltrexone, an opioid antagonist, is known to reduce ethanol consumption.
• The specific neuroplastic adaptations in the brain underlying this reduction are not fully understood.

Purpose of the Study:

• To identify gene transcription alterations responsible for naltrexone's attenuation of voluntary ethanol intake in rats.
• To elucidate the role of specific genes and brain regions in naltrexone's effect on ethanol consumption.

Main Methods:

• Rats with high ethanol preference were administered increasing doses of naltrexone.
• Gene expression levels of various neurochemical markers were analyzed in specific brain regions.

Main Results:

• Naltrexone significantly decreased voluntary ethanol intake by 50%.
• Ethanol consumption altered the expression of mu-opioid receptor, tyrosine hydroxylase (TH), proenkephalin (PENK), corticotropin releasing factor (CRF), cannabinoid CB(1) receptor (CB1-R), and serotonin transporter (5-HTT) in multiple brain regions.
• Naltrexone treatment blocked or reduced these ethanol-induced gene expression changes.

Conclusions:

• Naltrexone's reduction of ethanol intake is associated with the normalization of gene expression changes in brain regions critical for drug dependence.
• Mu-opioid receptor, TH, PENK, CRF, CB1-R, and 5-HTT genes play a role in the neuroadaptive mechanisms modulated by naltrexone in decreasing ethanol intake.